Atrasentan is a potent and selective antagonist for the endothelin A (ETA) receptor. It previously was evaluated in clinical trials for the treatment of prostate cancer and is now being evaluated in clinical trials for the treatment of chronic kidney disease associated with Type II diabetes.
The compound atrasentan was first reported in U.S. Pat. No. 5,767,144. Subsequently, several published international applications reported atrasentan monohydrochloride salts. WO2006/034085 reports amorphous atrasentan monohydrochloride. WO2006/034094 reports crystalline Form I of atrasentan monohydrochloride. WO2006/034084 reports crystalline Form II of atrasentan monohydrochloride. WO2006/034234 reports crystalline Form III of atrasentan monohydrochloride.
The preparation of atrasentan monohydrochloride and corresponding pharmaceutical formulations containing atrasentan monohydrochloride presents a number of manufacturing challenges that are discussed in greater detail below. There is a present need for pharmaceutically acceptable, alternative salts of atrasentan that reduce or eliminate the manufacturing challenges encountered with respect to the monohydrochloride salt.